Amanda Holck1, Owen M Wolkowitz2, Sindy H Mellon3, Victor I Reus2, J Craig Nelson2, Åsa Westrin1, Daniel Lindqvist4. 1. Lund University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry, Lund, Sweden. 2. Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA. 3. Department of OB/GYN and Reproductive Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA. 4. Lund University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry, Lund, Sweden; Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA. Electronic address: daniel.lindqvist@med.lu.se.
Abstract
BACKGROUND: Less than half of patients with major depressive disorder (MDD) respond to their first antidepressant trial. Our understanding of the underlying mechanisms of selective serotonin reuptake inhibitors (SSRIs) remains poor, and there is no reliable method of predicting treatment response. METHODS: Thirty-seven MDD subjects and 41 healthy controls, somatically healthy and medication-free for at least six weeks, were recruited, and plasma serotonin (5-HT) levels were assessed at baseline. Twenty-six of the MDD subjects were then treated in an open-label manner with clinically appropriate doses of sertraline for 8 weeks, after which plasma 5-HT levels were again assessed. Response to treatment was defined as an improvement of 50% or more on the Hamilton Depression Rating Scale. RESULTS: Non-responders to sertraline treatment had significantly lower pre-treatment 5-HT levels compared to both healthy controls and responders (F = 4.4, p = 0.004 and p = 0.036, respectively). There was a significant decrease in 5-HT levels over treatment in all MDD subjects (t = 6.2, p = 0.000003). The decrease was significantly more prominent in responders compared to non-responders (t = 2.1, p = 0.047). There was no significant difference in post-treatment 5-HT levels between responders and non-responders. LIMITATIONS: The study had a modest sample size. 5-HT levels in plasma may not reflect 5-HT levels in the brain. CONCLUSIONS: The results indicate that SSRI response may be facilitated by adequate baseline plasma 5-HT content and that successful SSRI treatment is associated with greater decreases in circulating 5-HT. Plasma 5-HT content may be a predictor of SSRI treatment outcome. Potential underlying mechanisms are discussed.
BACKGROUND: Less than half of patients with major depressive disorder (MDD) respond to their first antidepressant trial. Our understanding of the underlying mechanisms of selective serotonin reuptake inhibitors (SSRIs) remains poor, and there is no reliable method of predicting treatment response. METHODS: Thirty-seven MDD subjects and 41 healthy controls, somatically healthy and medication-free for at least six weeks, were recruited, and plasma serotonin (5-HT) levels were assessed at baseline. Twenty-six of the MDD subjects were then treated in an open-label manner with clinically appropriate doses of sertraline for 8 weeks, after which plasma 5-HT levels were again assessed. Response to treatment was defined as an improvement of 50% or more on the Hamilton Depression Rating Scale. RESULTS: Non-responders to sertraline treatment had significantly lower pre-treatment 5-HT levels compared to both healthy controls and responders (F = 4.4, p = 0.004 and p = 0.036, respectively). There was a significant decrease in 5-HT levels over treatment in all MDD subjects (t = 6.2, p = 0.000003). The decrease was significantly more prominent in responders compared to non-responders (t = 2.1, p = 0.047). There was no significant difference in post-treatment 5-HT levels between responders and non-responders. LIMITATIONS: The study had a modest sample size. 5-HT levels in plasma may not reflect 5-HT levels in the brain. CONCLUSIONS: The results indicate that SSRI response may be facilitated by adequate baseline plasma 5-HT content and that successful SSRI treatment is associated with greater decreases in circulating 5-HT. Plasma 5-HT content may be a predictor of SSRI treatment outcome. Potential underlying mechanisms are discussed.
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